Kruglov lab

Interaction of immune system and microbiota in chronic inflammation

Introduction
Members
Cooperation partners
Selected Publications

There is a clear indication that rheumatic diseases, such as rheumatoid arthritis, ankylosing spondylitis and Crohn’s disease, can be influenced by commensal microorganisms, but mechanistic aspects of microbiota contribution to the disease development, pathogenesis, and chronicity remain to be determined. We postulate that microbiota changes might modulate cytokines production and activation of the immune system in the development of chronic rheumatic diseases.

Proinflammatory cytokine production can be influenced by microbiota composition in rheumatic patients. We observed significant changes in microbiota composition in patients with rheumatic diseases, and enhanced capacity of such microbiota to induce Tumor Necrosis Factor (TNF) production from peripheral blood mononuclear cells. TNF blockade in patients leads to significant disease amelioration and tissue repair via poorly understood mechanisms. We have revealed that TNF blocks tissue repair via the downregulation of IL-22 biological activity both in mice and humans. In chronic autoimmune arthritis, we found that TNF is crucial for the regulation of blood monocyte homeostasis via control of T cell responses.

Since one of the mechanisms of immune-mediated control of microbiota composition is the production of microbiota-specific IgA antibodies by intestinal plasma B cells, we are currently  dissecting the mechanisms of microbiota control by IgA and utilisation of these mechanisms for microbiota analysis and modulation. To this end, we have generated a set of microbiota-specific IgA antibodies specific to distinct microbiota species, and have identified several antibodies that bind immunologically relevant bacteria in the microbiota.

Altogether, our data reveal interplay between microbiota composition, cytokine production and rheumatic diseases manifestation, and provide potential novel strategies for treating rheumatic diseases by modulating intestinal microbiota.

Group Leader
    Dr. Andrey Kruglov

Dr. rer. nat. Andrey Kruglov

Deutsches Rheuma-Forschungszentrum Berlin
Chronische Entzündung
Charitéplatz 1
10117 Berlin

Tel. +49 (0)30 28460-641/643
Fax +49 (0)30 28460-603
kruglov@drfz.de

Keywords
Microbiota
Chronic inflammation
Cytokines

Continue to Members

Group leader
Dr. rer. nat. Andrey Kruglov

Students
Justus Ninnemann, PhD student
Katharina Kurz, PhD student
Julia Röchert, Master student
Sarah Khedhayir, Bachelor student

Group Leader
    Dr. Andrey Kruglov

Dr. rer. nat. Andrey Kruglov

Deutsches Rheuma-Forschungszentrum Berlin
Chronische Entzündung
Charitéplatz 1
10117 Berlin

Tel. +49 (0)30 28460-641/643
Fax +49 (0)30 28460-603
kruglov@drfz.de

Keywords
Microbiota
Chronic inflammation
Cytokines

Continue to Cooperation partners

• Prof. Dr. Mathias Heikenwälder DKFZ, Heidelberg, Germany
• Dr. Anja Kühl Charite, Campus Benjamin Franklin, Berlin, Germany
• Prof. Dr. Stefan Kaufmann, MPIIB, Berlin, Germany
• Prof. Dr. Britta Siegmund, Charite, Campus Benjamin Franklin, Berlin, Germany
• Prof. Dr. Dennis Poddubny, Charite, Campus Benjamin Franklin, Berlin, Germany
• Prof. Dr. Paul Friedemann, Charite, Berlin, Germany
• Prof. Dr. Bastian Opitz, Charite, Campus Benjamin Franklin, Berlin, Germany
• Prof. Dr. Ivaylo Ivanov, Columbia University, New York, USA
• Prof. Dr. Sergei Grivennikov, Fox Chase Cancer Center, Philadelphia, USA
• Prof. Dr. Harald Prüß, Charite, Berlin, Germany
• Prof. Dr. Thomas Kammertoens, MDC, Berlin, Germany

Group Leader
    Dr. Andrey Kruglov

Dr. rer. nat. Andrey Kruglov

Deutsches Rheuma-Forschungszentrum Berlin
Chronische Entzündung
Charitéplatz 1
10117 Berlin

Tel. +49 (0)30 28460-641/643
Fax +49 (0)30 28460-603
kruglov@drfz.de

Keywords
Microbiota
Chronic inflammation
Cytokines

Continue to Selected Publications
  1. Neumann C, Blume J, Roy U, Teh PP, Vasanthakumar A, Beller A, Liao Y, Heinrich F, Arenzana TL, Hackney JA, Eidenschenk C, Gálvez EJC, Stehle C, Heinz GA, Maschmeyer P, Sidwell T, Hu Y, Amsen D, Romagnani C, Chang HD, Kruglov A, Mashreghi MF, Shi W, Strowig T, Rutz S, Kallies A, Scheffold A. c-Maf-dependent Tregcell control of intestinal TH17 cells and IgA establishes host-microbiota homeostasis. Nat Immunol. 2019 Apr;20(4):471-481.
  2. Mazzoni A, Maggi L, Siracusa F, Ramazzotti M, Rossi MC, Santarlasci V, Montaini G, Capone M, Rossettini B, De Palma R, Kruglov A, Chang HD, Cimaz R, Maggi E, Romagnani S, Liotta F, Cosmi L, Annunziato F. Eomes controls the development of Th17-derived (non-classic) Th1 cells during chronic inflammation. Eur J Immunol. 2019 Jan;49(1):79-95.
  3. Atretkhany KN, Mufazalov IA, Dunst J, Kuchmiy A, Gogoleva VS, Andruszewski D, Drutskaya MS, Faustman DL, Schwabenland M, Prinz M, Kruglov AA, Waisman A, Nedospasov SA Intrinsic TNFR2 signaling in T regulatory cells provides protection in CNS autoimmunity. Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):13051-13056.
  4. Robak OH, Heimesaat MM, Kruglov AA, Prepens S, Ninnemann J, Gutbier B, Reppe K, Hochrein H, Suter M, Kirschning CJ, Marathe V, Buer J, Hornef MW, Schnare M, Schneider P, Witzenrath M, Bereswill S, Steinhoff U, Suttorp N, Sander LE, Chaput C, Opitz B. Antibiotic treatment-induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia. J Clin Invest. 2018 Jul 16. pii: 97065. doi: 10.1172/JCI97065.
  5. Korneev KV, Kondakova AN, Sviriaeva EN, Mitkin NA, Palmigiano A, Kruglov AA, Telegin GB, Drutskaya MS, Sturiale L, Garozzo D, Nedospasov SA, Knirel YA, Kuprash DV. Hypoacylated LPS from Foodborne Pathogen Campylobacter jejuni Induces Moderate TLR4-Mediated Inflammatory Response in Murine Macrophages. Front Cell Infect Microbiol. 2018 Feb 27;8:58. doi: 10.3389/fcimb.2018.00058
Group Leader
    Dr. Andrey Kruglov

Dr. rer. nat. Andrey Kruglov

Deutsches Rheuma-Forschungszentrum Berlin
Chronische Entzündung
Charitéplatz 1
10117 Berlin

Tel. +49 (0)30 28460-641/643
Fax +49 (0)30 28460-603
kruglov@drfz.de

Keywords
Microbiota
Chronic inflammation
Cytokines

Continue to
Chronic inflammation Dr. Andrey Kruglov kruglov@drfz.de more
Group Leader
    Dr. Andrey Kruglov

Dr. rer. nat. Andrey Kruglov

Deutsches Rheuma-Forschungszentrum Berlin
Chronische Entzündung
Charitéplatz 1
10117 Berlin

Tel. +49 (0)30 28460-641/643
Fax +49 (0)30 28460-603
kruglov@drfz.de

Keywords
Microbiota
Chronic inflammation
Cytokines

Continue to Introduction